Disazo compound for therapeutic use



Patented Nov. 6, 1934 .1; 1 979 534 DISAZO COMPOUND FOR THERAPEUTIC USE Joseph Ebert, Westmont, N. J., assignor to The Farastan Company, Philadelphia, Pa., a cornotation of Pennsylvania No Drawing. Application (lctober 15, 1931,

. SerialNo. 569,119

19 Claims. (o1. 260-46) This invention relates to new disazo compounds hydrochlorides andsulfates are more or less freeior therapeutic use. It includes the new com- 1y soluble in Water. The low toxicity of these pounds, therapeutic compositions comprising compounds, their colloidal character and their these new compounds, and the method of preparcolor make them particularly advantageous for ingthe new compounds. use in the, treatment of intestinal and. genito- In order to produce disazo compounds having urinary disorders. The compounds may be used the desirable therapeutic properties of the com in the form of their alkali salts, their hydrochlopoundsof this invention, it has been found necesrides, their sulfates, or their free bases, all of sary to couple ,adisazotizeddiamine nucleus with which are soluble :in the common organic sol- IO a substituted aromatic amine and a substituted vents, such as ethyl alcohol and other alcohols aromatic carboxylic acid. The substituted aroand acetone. matic amine may be either an alkoxy amine or .a The following examples illustrate the invention, diamine such as but it is intended and is to be understood that the invention is not limited to the specific examl5 C6H4(NH2)OCH3 ples given below. .In connection withExamplel {T9 or the method of preparation is given somewhat in C H4(NI- I2 2. detail. Theother examples may be prepared by it maycontain other substituents such as tetrazotizing one molecular weight of the diamino The substituted aromatic carboxyllc acid may be nucleus andrfcoupling this with one molecular an aromatic ammo carboxylic acid or an aromatic Weight of a substituted amine (either an alkoxy 75 hydroxy'carboxyhc such as amine'or 'diamine), and onemolecular weight'of CsH4(OH)COOH an aromatic carboxylic acid (either an amino or p v v carboxylic acid or anhydroxy carboxylic acid). Thecompounds which are obtained as salts,,,for 25 G M QCO example sodium salts, may be purified and the 3p hydrochloridesor=sulfates= orthe free bases may g igg g gfi i ammo group and be .formed from the salts in the manner \wellp i v p known inthe art. y

C-I-Ie' NI-Iz'(OH)C00 The nucleus of each of=the=disazo compounds of the first eight examples is diphenyl. These 3g compounds are prepared bytetrazotizing benzi- 3C dine. The tetrazo nuclei or Examples 9 and 10 are modified diphenyl groups. The nuclei of Exa, .fizngl gz sii dif, i ai r g z 1 ggg bfi i d2? amples 11 and 12 is the phenylene group,,-and7.the phenyl methane residue. The residue may connuclel of p 3 and 144s t j l tain alkyl or alkoxy substituents, for examplex m are Prepared by 'zfm diamino derivatives of d1pheny1 methane or-mod- The diSELZO compoundsofthis invention are 110 Sodium salt of diphenyl-disazo-o;ethoxy-amino phenol-o- 100 r b i d toxic. They contain no nltro, sulion1c, chlor1ne, f bromine or iodine 18.6 parts by weight of benzidine are heated wlth The disazo compounds of this invention possess 30 p s of C nc ted hydrochloric acid,-(or pronounced bacetricidalandbacteriostatic value the correspondlns a u t f benzldlne ydr .50 and have a distinct analgesic action. The bac-Q ..chloride may b used) a dissolved p m5 tericidal value isat least lto i500 and-the baced in approximately 250 parts of water. The teriostatic value is at least 1 to 2000. The comsolution is tetrazotized with a solution of 14.2 pounds are yellow to brown in color, for example parts of sodium nitrite in parts of water keepyellowish brown or reddish brown. Theiralkali ing the temperature at approximately l5feC.

51S salts are practically insoluble in water but their This tetrazo solution is then coupledwith a no solution of 14 parts of o-phenetidine in 12 parts of concentrated hydrochloric acid and 150 parts of water mixed with a solution of 14 parts of o-amino benzoic acid in 12 parts of concentrated hydrochloric acid and 100 parts of water. The coupling is carried out at a temperature of approximately 15 to 25 C. The solution is then made alkaline by the addition of a 10 to 20 percent sodium hydroxide solution. The sodium salt of the new disazo compound separates out as a yellowish-brown precipitate. This precipitate is washed with water until free from chloride and then dried. The compound is purified by recrystallization from ethyl alcohol.

Example 2 1) NH: 0 o 0 Na (2) Sodium salt of di henyLdisazo-o-ethoxy amino phenol-oydroxybenzoic acid This compound is prepared from benzidine, ophenetidine and salicylic acid.

Example 7 Sodium salt of diphenyl-disazddi amino bcnzene-o-hydroxy benzoic acid This compound is made from benzidine, mphenylene diamine, and salicylic acid.

Example 8 of diphenyl-disazo-diamino-bcnzcne-amino hydroxy benzoic acid Sodium salt Example 9 (2) C 5H5- O Example 3 (2) O2H5 O NH2 C gHrN=N-CoHrC uH4-N=NC uHzO 11(1) (D I CO 0Na(2) Sodium salt of diphenyl-disazo-o-ethoxy-amino phenolamino hydroxybenzoic acid OOONa(2) Sodium salt of dimethoxy-diphenyl-disazo-o-ethoxy-amino plienol-o-amino benzoic acid This compound is made from dianisidine, o-phenetidine and o-amino benzoic acid.

Example 1 0 Example 5 C2H5' o 0 11(2) OeHrN=N-C gH4-CcH4-N=NCHr-C H (5) (1)NH: C O O Na (1) Sodium salt of diphenyl-disazo-o-ethoxy-amino phenol-phydroxymetatoluic acid This compound is made from benzidine, o-phene tidine and p-cresotic acid.

Example 6 (DN NH2(1) O u a-N=NCaH4- oH4-N=N-C SE3 N 0 o ONa 2) Sodium salt of diphenyl-disazo-diamino-benzene-o-amino benzoic acid Mir- This compound is made from benzidine, m-phenylene diamine and o-amino benzoic acid.

COONa(2) Sodium salt of (lito1yl-disazo-o-ethoxy-amino phenol-o-amino benzoic acid This compound is made from o-tolidine, o-phenetidine and o-amino benzoic acid.

Example 11 CoHa-N=N 1 -06H4- (a N=NO 1H3 NH: 0 o ONa(2) Sodium salt of benzene-disazq-o-etlloxy-amino phenol-oamino benzoic acid This compound is made from m-phenylene diamine, o-phenetidine and o-amino benzoic acid.

Sodium salt of benzenc-disazo-diamino bcnzene-amiuohydroxy benzoic acid This compound is made by tetrazotizing mphenylene diamine and coupling with m-phenylene diamine and 5-amino hydroxy benzoic acid.

Example 13 Sodium salt of toluene-disazo;o-ethoxy-amino phenol-oamuio bcnzoic acid This compound is made from m-toluyle'ne di- Sodiumsalt of toluene-disazo-diamino benzenembfdroxy benzoic acid This compound is made from m-toluyl'ene diamine, m-phenylene diamineand o-hydroxy ben- Sodiuin' salt of diphenyl methane;disazo-o-etlioxy amino phenol-o-amino benzoic acid V zoic acid.

, Exampleld (3)NHI' eHa -N=N(l)--G,H -CHr-G5H;-(1)N=N-Oqfla (1mm Sodium salt of dighenyl methane-disazo-diamino-benzenew ydroxy benzoic acid This compound is made from p-p'-diamino diphenyl methane, m-phenylene diamine, and ohydroxy benzoic acid.

Example 17 (2) Cilia-0 diphenyl methaneresidue, R is-an alkoxy-aromatic aminenndR is an aminocarboxylic acid or an aminocarboxylate both R and R" being of the benzene series.

ooomey v 4. A non-toxic disazd compound having the general formulaR"-N'=NR-N=N-R" where Risa phenyl'residue, a diphenyl residue ora "Z010, acid. diphenyl methane residue, R is an aromatic di- Emmple 15, amine and R is an hydroxy monocarboxylic "(c map w a 1935(1) o.m--N=N(1)-'-ou1.o11.o.H;--(1)N=N .H=

. a (1mm 000mm acid or an hydroxymonocarboxylate both R and R being of the benzene series.

=5. Anon-toxic disazo compound having the generalformula R -N=N-R-N==N--R where This a phenyl residue, a diphenyl residue on a diphenyl methane residue, where R' is an alkoxy aromatic amiiie and R is an hydroxy carboxylic acid o r-an hydroxy carboxy-latebotl'i' Handle" being of the benzene series.

6. A non-toxic disazo compound having the general formula RN=NRN=N-R" where C uHrN=N (1) C 011 O C 1135 (2) O Hr-C 112- O O H (2) (1) N=N- C H:- 0 H (1) Sodium salt of diphenyl methane-diethoxy-disazo-o-ethoxyamino phenol-amino hydroxy benzoic acid This compound is made from diamino-diethoxydiphenyl methane, o-phenetidine, and 5-amin0 hydroxy benzoic acid.

Example 18 Sodium salt of diphenyl methane-diethoxy-disazo-diamino benzene-o-amino benzoic acid This compound is made from diamino-diethoxydiphenyl methane, m-phenylene diamine and 0- amino benzoic acid.

I claim:

1. A non-toxic disazo compound having the general formula RN=N-RN=NR" where R is a phenyl residue, 2. diphenyl residue, or a diphenyl methane residue, R is an aromatic diamine or an alkoxy aromatic amine and R is an amino or hydroxy monocarboxylic acid or an amino or hydroxy monocarboxylate both R and R being of the benzene series.

2. A non-toxic disazo compound having the general formula R-N=N-RN=NR" where R is a phenyl residue, a diphenyl residue or a diphenyl methane residue, R is an aromatic diamine and. R is an amino monocarboxylic acid or an amino monocarboxylate both R and R being of the benzene series.

3. A non-toxic disazo compound having the general formula RN=NR-N=NR where R is a phenyl residue, a diphenyl residue or a GOONa(2) 7. A non-toxic diazo compound having the general formula RN=N-RN=NR" where R is a diphenyl residue, R is an aromatic diamine or an alkoxy aromatic amine, and R is an amino or hydroxy carboxylic acid or an amino or hydroxy carboxylate both R and R" being of the benzene series.

8. A non-toxic disazo compound having the sodium salt of benzene-disazo-o-- to '1500 and a bacteriostatic value of at least 1; to

a pound, which comprises tetrazotizing a diamino 2000 and having the general formula- R' N =NRN NR" where R is a phenyl residue a diphenyl residue or a diphenyl methane residue, R, is an aromatic diamine or an alkoxy aromatic amine and R is an amino or hydroxy monocarboxylic acid or an amino or hydroxy monocarboxylate both R. and B" being of the benzene series.

13. The method of preparing a disazo compound, which comprises tetrazotizing a diamino compound having a nucleus belonging to the group consisting of phenyl, diphenyl and diphenyl methane residues and coupling the tetrazotized compound with an aromatic diamine of the benzene series and an amino monocarboxylic acid of the benzene series.

14. The method of preparing a disazo compound, which comprises tetrazotizing a diamine compound having a nucleus belonging to the group consisting of phenyl, diphenyl, and 'diphenyl methane residues and coupling the tetraz'otized compound with an alkoxy aromatic amine of the benzene series and an amino carboxylic acid of the benzene series.

15. The method of preparing a disazo compound, which comprises tetrazotizing a diamine compound having a nucleus belonging to the group consisting of phenyl, diphenyl, and. diphenyl methane residues and coupling the tetrazotized compound with an aromatic diamine of the benzene series and an hydroxy monocarboxylic acid of the benzene series.

16., The method of preparing a disazo comcompound having a nucleus belonging to the group consisting oi phenyl, diphenyl, and diphenyl methane residues and coupling the tetrazotized diamine with an alkoxy aromatic amine of the benzene series and an hydroxy carboxylic acid of the benzene series.

17. A non-toxic disazo compound having the general formula- R--N=NR-N=NR" where R is a phenyl residue, a diphenyl residue or a diphenyl methane residue, R is an alkoxy aromatic amine and R" is an amino-mono-carboxylic acid or an amino-mono-carboxylate, both R and R" being of the benzene series.

18. A non-toxic disazo compound having the general formula R. N =NR N= NR" where R. is 'a phenyl residue, a""diphenyl residue or a diphenyl methane residue, R is a diamine or alkoxy amine of; the benzene series and R" is a benzene nucleus substituted only with an amino .or hydroxy, or amino and hydroxy group, and one carboxylic acid or carboxylate group.

19. The method of preparing a disazo compound which comprises tetrazotizing a diamino compound having a nucleus belonging to the group consisting of phenyl, diphenyl and diphenyl methane residues and coupling the tetrazotized compound with an alkoxy aromatic amine ofthe benzene series and an amino-mono-carboxylic acid of the benzene series.

JOSEPH EBERT. 

